The regulation of translation in alphavirus-infected cells

Sindbis virus (SINV) contains an RNA genome of positive polarity with two open reading frames (ORFs). The first ORF is translated from the genomic RNA (gRNA), rendering the viral non-structural proteins, whereas the second ORF is translated from a subgenomic mRNA (sgRNA), which directs the synthesis...

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Authors: Carrasco, Luís, Sanz, Miguel Ángel, González-Almela, Esther
Format: article
Status:Published version
Publication Date:2018
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/182404
Online Access:http://hdl.handle.net/10261/182404
Access Level:Open access
Keyword:IRES
RNA structure
Initiation factors
Alphaviruses
Regulation of translation
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spelling The regulation of translation in alphavirus-infected cellsCarrasco, LuísSanz, Miguel ÁngelGonzález-Almela, EstherIRESRNA structureInitiation factorsAlphavirusesRegulation of translationSindbis virus (SINV) contains an RNA genome of positive polarity with two open reading frames (ORFs). The first ORF is translated from the genomic RNA (gRNA), rendering the viral non-structural proteins, whereas the second ORF is translated from a subgenomic mRNA (sgRNA), which directs the synthesis of viral structural proteins. SINV infection strongly inhibits host cell translation through a variety of different mechanisms, including the phosphorylation of the eukaryotic initiation factor eIF2α and the redistribution of cellular proteins from the nucleus to the cytoplasm. A number of motifs have been identified in SINV sgRNA, including a hairpin downstream of the AUG initiation codon, which is involved in the translatability of the viral sgRNA when eIF2 is inactivated. Moreover, a 3′ -UTR motif containing three stem-loop structures is involved in the enhancement of translation in insect cells, but not in mammalian cells. Accordingly, SINV sgRNA has evolved several structures to efficiently compete for the cellular translational machinery. Mechanistically, sgRNA translation involves scanning of the 5′ -UTR following a non-canonical mode and without the requirement for several initiation factors. Indeed, sgRNA-directed polypeptide synthesis occurs even after eIF4G cleavage or inactivation of eIF4A by selective inhibitors. Remarkably, eIF2α phosphorylation does not hamper sgRNA translation during the late phase of SINV infection. SINV sgRNA thus constitutes a unique model of a capped viral mRNA that is efficiently translated in the absence of several canonical initiation factors. The present review will mainly focus in the non-canonical mechanism of translation of SINV sgRNA.DGICYT (Dirección General de Investigación Científica y Técnica, Ministerio de Economía y Competitividad, Spain) grant (SAF2015-66170-R (MINECO/FEDER)) to LC. EGA is the holder of an FPU (Formación de Personal Universitario) Fellowship (FPU15/05709). Institutional grants from the Fundación Ramón Areces and Banco de Santander to the Centro de Biología Molecular “Severo Ochoa” (CSIC-UAM)Peer ReviewedMultidisciplinary Digital Publishing InstituteDirección General de Enseñanza Superior e Investigación Científica (España)Banco SantanderFundación Ramón ArecesMinisterio de Economía y Competitividad (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2019201920182019info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/182404reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1824042026-05-22T06:33:51Z
dc.title.none.fl_str_mv The regulation of translation in alphavirus-infected cells
title The regulation of translation in alphavirus-infected cells
spellingShingle The regulation of translation in alphavirus-infected cells
Carrasco, Luís
IRES
RNA structure
Initiation factors
Alphaviruses
Regulation of translation
title_short The regulation of translation in alphavirus-infected cells
title_full The regulation of translation in alphavirus-infected cells
title_fullStr The regulation of translation in alphavirus-infected cells
title_full_unstemmed The regulation of translation in alphavirus-infected cells
title_sort The regulation of translation in alphavirus-infected cells
dc.creator.none.fl_str_mv Carrasco, Luís
Sanz, Miguel Ángel
González-Almela, Esther
author Carrasco, Luís
author_facet Carrasco, Luís
Sanz, Miguel Ángel
González-Almela, Esther
author_role author
author2 Sanz, Miguel Ángel
González-Almela, Esther
author2_role author
author
dc.contributor.none.fl_str_mv Dirección General de Enseñanza Superior e Investigación Científica (España)
Banco Santander
Fundación Ramón Areces
Ministerio de Economía y Competitividad (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv IRES
RNA structure
Initiation factors
Alphaviruses
Regulation of translation
topic IRES
RNA structure
Initiation factors
Alphaviruses
Regulation of translation
description Sindbis virus (SINV) contains an RNA genome of positive polarity with two open reading frames (ORFs). The first ORF is translated from the genomic RNA (gRNA), rendering the viral non-structural proteins, whereas the second ORF is translated from a subgenomic mRNA (sgRNA), which directs the synthesis of viral structural proteins. SINV infection strongly inhibits host cell translation through a variety of different mechanisms, including the phosphorylation of the eukaryotic initiation factor eIF2α and the redistribution of cellular proteins from the nucleus to the cytoplasm. A number of motifs have been identified in SINV sgRNA, including a hairpin downstream of the AUG initiation codon, which is involved in the translatability of the viral sgRNA when eIF2 is inactivated. Moreover, a 3′ -UTR motif containing three stem-loop structures is involved in the enhancement of translation in insect cells, but not in mammalian cells. Accordingly, SINV sgRNA has evolved several structures to efficiently compete for the cellular translational machinery. Mechanistically, sgRNA translation involves scanning of the 5′ -UTR following a non-canonical mode and without the requirement for several initiation factors. Indeed, sgRNA-directed polypeptide synthesis occurs even after eIF4G cleavage or inactivation of eIF4A by selective inhibitors. Remarkably, eIF2α phosphorylation does not hamper sgRNA translation during the late phase of SINV infection. SINV sgRNA thus constitutes a unique model of a capped viral mRNA that is efficiently translated in the absence of several canonical initiation factors. The present review will mainly focus in the non-canonical mechanism of translation of SINV sgRNA.
publishDate 2018
dc.date.none.fl_str_mv 2018
2019
2019
2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/182404
url http://hdl.handle.net/10261/182404
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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